Paternal high protein diet modulates body composition, insulin sensitivity, epigenetics, and gut microbiota intergenerationally in rats

Chleilat, Faye; Schick, Alana; Deleemans, Julie; Ma, Kyle; Alukic, Erna; Wong, Jennifer; Tuplin, Erin W. Noye; Nettleton, Jodi E.; Reimer, Raylene A.

doi:10.1096/fj.202100198rr

Cited by 20 publications

(15 citation statements)

References 71 publications

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“…However, the controversial role of mucin in different diseases might determine the diverse effect of Akkermansia (Cabrera-Rubio et al, 2019;Xie and Fei, 2021). For example, Akkermansia muciniphila was recommended as the promising probiotic against metabolic disorders (Zhang et al, 2019), while the studies in a high-fructose (Wang et al, 2020) or high-fat diet showed the increase of Akkermansia (Xie and Fei, 2021), and Akkermansia could reduce the important enzymes which prevented hyperglycemia and hyperlipidemia (Chleilat et al, 2021). Besides, the enrichment of Akkermansia has been reported in inflammatory states such as alcohol-induced steatohepatitis (Ran et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Dynamic Alterations of the Gut Microbial Pyrimidine and Purine Metabolism in the Development of Liver Cirrhosis

Xiong

Shao

et al. 2022

Front. Mol. Biosci.

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Background: Liver cirrhosis is the common end-stage of liver disease which lacks effective treatment, thus studies to determine prevention targets are an urgent need. The intestinal microbiota (IM) play important roles in modulating liver diseases which are mediated by microbial metabolites. Despite decades of growing microbial studies, whether IM contribute to the development of cirrhosis and the intimate metabolic link remain obscure. Here, we aimed to reveal the dynamic alterations of microbial composition and metabolic signatures in carbon tetrachloride (CCl4)-induced liver cirrhosis mice.Methods: CCl4-treated mice or normal control (NC) were sacrificed (n = 10 per group) after 5 and 15 weeks of intervention. The disease severity was confirmed by Masson’s trichrome or Sirius red staining. Metagenomics sequencing and fecal untargeted metabolomics were performed to evaluate the composition and metabolic function of IM in parallel with the development of cirrhosis.Results: The CCl4-treated mice presented liver fibrosis at 5 weeks and liver cirrhosis at 15 weeks indicated by collagen deposition and pseudo-lobule formation, respectively. Mice with liver cirrhosis showed distinct microbial composition from NC, even in the earlier fibrosis stage. Importantly, both of the liver fibrosis and cirrhosis mice were characterized with the depletion of Deltaproteobacteria (p < 0.05) and enrichment of Akkermansia (p < 0.05). Furthermore, fecal metabolomics revealed distinguished metabolomics profiles of mice with liver fibrosis and cirrhosis from the NC. Notably, pathway enrichment analysis pointed to remarkable disturbance of purine (p < 0.001 at 5 weeks, p = 0.034 at 15 weeks) and pyrimidine metabolic pathways (p = 0.005 at 5 weeks, p = 0.006 at 15 weeks) during the development of liver cirrhosis. Interestingly, the disorders of pyrimidine and purine metabolites like the known microbial metabolites thymidine and 2′-deoxyuridine had already occurred in liver fibrosis and continued in cirrhosis.Conclusion: These novel findings indicated the crucial role of IM-modulated pyrimidine and purine metabolites in the development of liver cirrhosis, which provides microbial targets for disease prevention.

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Section: Discussionmentioning

confidence: 99%

Dynamic Alterations of the Gut Microbial Pyrimidine and Purine Metabolism in the Development of Liver Cirrhosis

Xiong

Shao

et al. 2022

Front. Mol. Biosci.

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“…Ethical approval was granted by the University of Calgary Animal Care Committee (Protocol#AC15-0079) and conformed to the Guide to the Care and Use of Experimental Animals. Obesity was induced in 8-week-old female Sprague-Dawley rats using a 10-week feeding period with a high fat/high sucrose diet (HFS, 39% fat and 44% sucrose, Dyets #102412), the composition of which has been previously published (17). Given that Sprague-Dawley rats can be obesity-prone or obesity-resistant when fed a HFS diet (18), we chose the top n = 45 best weight gainers from the n = 135 rats included in the diet-induced obesity protocol (Figure 1).…”

Section: Animals and Samplesmentioning

confidence: 99%

A Metagenomics Investigation of Intergenerational Effects of Non-nutritive Sweeteners on Gut Microbiome

et al. 2022

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To identify possible mechanisms by which maternal consumption of non-nutritive sweeteners increases obesity risk in offspring, we reconstructed the major alterations in the cecal microbiome of 3-week-old offspring of obese dams consuming high fat/sucrose (HFS) diet with or without aspartame (5–7 mg/kg/day) or stevia (2–3 mg/kg/day) by shotgun metagenomic sequencing (n = 36). High throughput 16S rRNA gene sequencing (n = 105) was performed for dams, 3- and 18-week-old offspring. Maternal consumption of sweeteners altered cecal microbial composition and metabolism of propionate/lactate in their offspring. Offspring daily body weight gain, liver weight and body fat were positively correlated to the relative abundance of key microbes and enzymes involved in succinate/propionate production while negatively correlated to that of lactose degradation and lactate production. The altered propionate/lactate production in the cecum of weanlings from aspartame and stevia consuming dams implicates an altered ratio of dietary carbohydrate digestion, mainly lactose, in the small intestine vs. microbial fermentation in the large intestine. The reconstructed microbiome alterations could explain increased offspring body weight and body fat. This study demonstrates that intense sweet tastants have a lasting and intergenerational effect on gut microbiota, microbial metabolites and host health.

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“…While the effects of HFD on individuals have been intensely studied over the past 30 years, the potential transgenerational impacts of HFD—more specifically, the impacts of paternal diet on obesogenic phenotypes in the offspring—are not well understood. Paternal HFD, leading to diet-induced obesity (DIO) in rats 3 – 5 , results in offspring with delayed growth, impaired liver function 6 – 10 , and deviations in social and anxiety-like defensive behavioral responses 11 , epigenetic reprogramming 12 , 13 , and alterations to the gut microbiome 14 , 15 . Recently, paternal diet has been implicated in the development of inter- and transgenerational offspring phenotypes 16 – 18 .…”

Section: Introductionmentioning

confidence: 99%

Effects of paternal high-fat diet and maternal rearing environment on the gut microbiota and behavior

Korgan

Foxx

Hashmi

et al. 2022

Sci Rep

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Exposing a male rat to an obesogenic high-fat diet (HFD) influences attractiveness to potential female mates, the subsequent interaction of female mates with infant offspring, and the development of stress-related behavioral and neural responses in offspring. To examine the stomach and fecal microbiome’s potential roles, fecal samples from 44 offspring and stomach samples from offspring and their fathers were collected and bacterial community composition was studied by 16 small subunit ribosomal RNA (16S rRNA) gene sequencing. Paternal diet (control, high-fat), maternal housing conditions (standard or semi-naturalistic housing), and maternal care (quality of nursing and other maternal behaviors) affected the within-subjects alpha-diversity of the offspring stomach and fecal microbiomes. We provide evidence from beta-diversity analyses that paternal diet and maternal behavior induced community-wide shifts to the adult offspring gut microbiome. Additionally, we show that paternal HFD significantly altered the adult offspring Firmicutes to Bacteroidetes ratio, an indicator of obesogenic potential in the gut microbiome. Additional machine-learning analyses indicated that microbial species driving these differences converged on Bifidobacterium pseudolongum. These results suggest that differences in early-life care induced by paternal diet and maternal care significantly influence the microbiota composition of offspring through the microbiota-gut-brain axis, having implications for adult stress reactivity.

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Paternal high protein diet modulates body composition, insulin sensitivity, epigenetics, and gut microbiota intergenerationally in rats

Cited by 20 publications

References 71 publications

Dynamic Alterations of the Gut Microbial Pyrimidine and Purine Metabolism in the Development of Liver Cirrhosis

Dynamic Alterations of the Gut Microbial Pyrimidine and Purine Metabolism in the Development of Liver Cirrhosis

A Metagenomics Investigation of Intergenerational Effects of Non-nutritive Sweeteners on Gut Microbiome

Effects of paternal high-fat diet and maternal rearing environment on the gut microbiota and behavior

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